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For the last year or so, we have been working on a book about pet food, What Pets Eat, to be published by Harcourt late in 2009. One of the pleasures of a long-term project like this is the time to follow digressions wherever they lead. Last year’s (2007) massive pet food recall was so much of a diversion that it resulted in a spin-off publication—Pet Food Politics:Chihuahua in the Coal Mine —scheduled for release this September by University of California Press.

The recall made us especially curious about the role of melamine, the substance responsible for kidney failure in pets eating food that supposedly contained wheat gluten. Just a glance at the chemical structure of melamine shows that it is high in nitrogen, a nutrient usually obtained from protein. This made us suspect that melamine must have been added deliberately to boost the apparent amount of protein in wheat gluten, because methods that measure the amount of protein in animal feed count nitrogen, not protein itself. Our suspicions were confirmed. The toxic “wheat gluten” turned out to be wheat flour laced with melamine.

But why would melamine harm cats and dogs? A quick search for studies of melamine toxicity turned up several performed on rats and mice, but just one on dogs (which dated from 1945).These studies gave the impression that melamine was not very toxic except at extremely high doses. Furthermore, the kidneys of animals who had eaten the contaminated food contained odd crystals that did not look like crystals of melamine.These turned out to be formed from complexes of melamine and one of its by-products, cyanuric acid. Even so, researchers and federal officials were puzzled. They had not heard of associations of melamine or cyanuric acid with kidney failure.

Really? Our Internet search turned up a brief and not particularly informative abstract of a 1960s study on melamine toxicity in sheep.We thought we needed to look at the entire paper, and found it and others in old bound journals in the Cornell library. These decades-old studies demonstrated that melamine is quite toxic, and causes kidney-related symptoms in animals at doses nearly identical to those reported in contaminated pet food. The studies were designed to test the idea that, because melamine nitrogen is far less expensive than protein nitrogen, melamine might have two useful purposes: (1) as an honest feed additive for ruminant animals, whose microorganisms can convert nonprotein nitrogen to amino acids, and (2) as a dishonest adulterant that makes feed test as though it contains more protein than it really does.

By following other leads,we also found references to relevant studies from the early 1980s in Italian journals that we had to request through interlibrary loan. These showed that melamine was so frequently used for fraudulent purposes in the 1980s that Italian scientists developed a test for it. They used the test to show that melaminna had been used to adulterate more than half the samples of fish meal they examined.

Most of the early information about melamine toxicity came from attempts to use it as a drug or nutrient. In the 1940s, investigators explored its potential as a canine diuretic. To follow what comes next, pay attention to the size of the melamine dose in milligrams per kilogram (mg/kg) of body weight, and recall that a kilogram is 2.2 pounds. The 1945 study showed that at a dose of about 120 mg/kg, dogs excreted crystals in their urine but otherwise did fine. In the 1960s, investigators used cyanuric acid (which is 32 percent nitrogen) to feed ruminant animals, and observed no problems even at high doses.Wouldn’t melamine (66.6 percent nitrogen) work even better?